Type 2 diabetes mellitus (T2DM) is the most common chronic diseases and high prevalence in worldwide. It was suggested in the recent long-term mega trials that intensive glycemic control was used to reduce the aggravation of insulin resistance, particularly in T2DM, and the risk of cardiovascular disease (CVD) (Avogaro, “Treating diabetes today with gliclazide MR: a matter of numbers.” Diabetes, obesity & metabolism 14 Suppl 1: 14-19, 2012). Accordingly, it is more desirable to develop the agents for glycemic control, than insulin analogous. For instance, sitagliptin that provides the effect for glycemic control has been developed as an agent for treating T2DM, which is a highly selective dipeptidyl peptidase-4 inhibitor (Goldstein et al., “Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes.” Diabetes Care 30(8): 1979-1987, 2007). Furthermore, metformin was reported to be effective for glycemic control by activating the AMP-activated protein kinase (AMPK) (Riddle, “Oral pharmacologic management of type 2 diabetes.” American Family Physician 60(9): 2613-2620, 1999; Zhou et al., “Role of AMP-activated protein kinase in mechanism of metformin action.” Journal of Clinical Investigation 108(8): 1167-1174, 2001; Fryer et al., “The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways.” Journal of Biological Chemistry 277(28): 25226-25232, 2002; Leverve et al., “Mitochondrial metabolism and type-2 diabetes: a specific target of metformin.” Diabetes and Metabolism 29(4 Pt 2): 6S88-94, 2003). Sitagliptin and metformin are widely used as first-line drugs for treatment of T2DM to reduce blood sugar levels through different mechanisms. In the previous clinical trials, the efficacy of initial combination therapy with sitagliptin and metformin was confirmed in patients with T2DM.
Some Chinese herbs have been reported to be potential to reduce blood glucose level (Lee et al., “Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states.” Diabetes 55(8): 2256-2264, 2006; Shi et al., “Tiliroside-derivatives enhance GLUT4 translocation via AMPK in muscle cells.” Diabetes research and clinical practice 92(2): e41-46, 2011). Cinnamomum kanehirai is one of species Lauraceae only from Taiwan (Wu et al., “Antrodia camphorata (“niu-chang-chih”), new combination of a medicinal fungus in Taiwan.” BOTANICAL BULLETIN-ACADEMIA SINICA TAIPEI 38: 273-276, 1997). Antrodia camphorate is a parasitic fungal on the inner cavity of C. kanehirae (Geethangili et al., “Review of Pharmacological Effects of Antrodia camphorata and Its Bioactive Compounds.” Evidence-Based Complementary and Alternative Medicine 2011: 212641, 2011).
It is still desirable to develop new drugs for treating T2DM and new process for chemical synthesis thereof.